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No association with the 5,10‐methylenetetrahydrofolate reductase gene and major depressive disorder: Results of the depression case control (DeCC) study and a meta‐analysis

No association with the 5,10‐methylenetetrahydrofolate reductase gene and major depressive... Unipolar major depressive disorder (MDD) is a complex disorder thought to result from multiple genes in combination with environmental and developmental components. The 5,10‐methylenetetrahydrofolate reductase gene (MTHFR) has been implicated in MDD in a meta‐analysis of association studies and is within a linkage region suggested by a recent study of affected sib pairs. A single base mutation in the MTHFR gene (C677T) results in the production of a mildly dysfunctional thermolabile enzyme. The MTHFR 677TT genotype, and to a lesser extent the 677CT genotype, is associated with a significant elevation in the circulating concentrations of homocysteine and a decrease in serum folate concentrations. This may parallel a similar reduction in 5‐methyltetrahydrofolate in the CNS, leading to a potential reduction in monoamine neurotransmitter function and an elevated risk of depressive disorder. To test the hypothesis that the MTHFR C677T polymorphism is involved in the predisposition to MDD, we conducted an association study of 1,222 patients with recurrent MDD and 835 control subjects. This allows 99% power to detect an effect of the size reported in the study of Bjelland et al. 2003, however no significant differences in genotype or allele frequencies between depressive patients and controls were observed. This was the case in the sample as a whole, and when females and males were considered separately. Our findings suggest that the MTHFR C677T polymorphism is not involved in the etiology of clinically significant recurrent MDD. © 2007 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Medical Genetics part B Wiley

No association with the 5,10‐methylenetetrahydrofolate reductase gene and major depressive disorder: Results of the depression case control (DeCC) study and a meta‐analysis

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References (49)

Publisher
Wiley
Copyright
Copyright © 2007 Wiley‐Liss, Inc.
ISSN
1552-4841
eISSN
1552-485X
DOI
10.1002/ajmg.b.30665
pmid
18165972
Publisher site
See Article on Publisher Site

Abstract

Unipolar major depressive disorder (MDD) is a complex disorder thought to result from multiple genes in combination with environmental and developmental components. The 5,10‐methylenetetrahydrofolate reductase gene (MTHFR) has been implicated in MDD in a meta‐analysis of association studies and is within a linkage region suggested by a recent study of affected sib pairs. A single base mutation in the MTHFR gene (C677T) results in the production of a mildly dysfunctional thermolabile enzyme. The MTHFR 677TT genotype, and to a lesser extent the 677CT genotype, is associated with a significant elevation in the circulating concentrations of homocysteine and a decrease in serum folate concentrations. This may parallel a similar reduction in 5‐methyltetrahydrofolate in the CNS, leading to a potential reduction in monoamine neurotransmitter function and an elevated risk of depressive disorder. To test the hypothesis that the MTHFR C677T polymorphism is involved in the predisposition to MDD, we conducted an association study of 1,222 patients with recurrent MDD and 835 control subjects. This allows 99% power to detect an effect of the size reported in the study of Bjelland et al. 2003, however no significant differences in genotype or allele frequencies between depressive patients and controls were observed. This was the case in the sample as a whole, and when females and males were considered separately. Our findings suggest that the MTHFR C677T polymorphism is not involved in the etiology of clinically significant recurrent MDD. © 2007 Wiley‐Liss, Inc.

Journal

American Journal of Medical Genetics part B – Wiley

Published: Sep 5, 2008

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